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Rapid progression of late onset axonal Charcot–Marie–Tooth disease associated with a novel MPZ mutation in the extracellular domain
  1. Matilde Laurà1,
  2. Micaela Milani1,
  3. Michela Morbin2,
  4. Maurizio Moggio3,
  5. Michela Ripolone3,
  6. Stefano Jann4,
  7. Vidmer Scaioli5,
  8. Franco Taroni1,
  9. Davide Pareyson1
  1. 1
    UO Biochimica e Genetica, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
  2. 2
    UO Neuropatologia, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
  3. 3
    Fondazione Ospedale Maggiore IRCCS, Centro Dino Ferrari, Università degli Studi di Milano, Milan, Italy
  4. 4
    Divisione di Neurologia, Ospedale Niguarda, Milan, Italy
  5. 5
    UO Neurofisiologia Clinica, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
  1. Dr Davide Pareyson, UO Biochimica e Genetica, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133 Milan, Italy; dpareys{at}


Myelin protein zero (MPZ) is a major component of compact myelin in peripheral nerves where it plays an essential role in myelin formation and adhesion. MPZ gene mutations are usually responsible for demyelinating neuropathies, namely Charcot–Marie–Tooth (CMT) type 1B, Déjèrine–Sottas neuropathy and congenital hypomyelinating neuropathy. Less frequently, axonal CMT (CMT2) associated with MPZ mutations has been described. We report six patients (one sporadic case and five subjects from two apparently unrelated families) with a late onset, but rapidly progressive, axonal peripheral neuropathy. In all patients, molecular analysis demonstrated a novel heterozygous missense mutation (208C>T) in MPZ exon 2, causing the Pro70Ser substitution in the extracellular domain. The diagnosis of CMT2 associated with MPZ mutations should be considered in both sporadic and familial cases of late onset, progressive polyneuropathy. The mechanism whereby compact myelin protein mutations cause axonal neuropathy remains to be elucidated.

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  • Funding: This work was supported by Telethon and Telethon-UILDM (grants GUP02169 to DP, GUP04009 to FT and GTF02008 to MM), Fondazione Pierfranco e Luisa Mariani (grant R-05-44 to FT), Associazione Amici del Centro Dino Ferrari-University of Milan and Eurobiobank project QLTR-2001-02769 (grants to MM).

  • Competing interests: None.

  • Abbreviations:
    myelin protein zero